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Objective:To study the effect of insulin intraperitoneal administration combined with dietary intervention on glycemic regulation in in KKAy mice with spontaneous type 2 diabetes.Methods:An animal model of type 2 diabetes was established, and healthy C57BL/6J mice were selected as the normal control group and healthy KKAy mice as the non-disease group. The successfully modeled KKAy mice were randomly divided into the subcutaneous group, the intraperitoneal group, and the untreated group. The non-disease group was given a maintenance diet, and all other groups were fed a high-fat, high-sugar diet. The daily feeding time was from 08:00 to 20:00, with one feeding at a 4-hour interval, for a total of four times. The subcutaneous and intraperitoneal groups were given subcutaneous and intraperitoneal insulin injections before feeding, and recombinant glargine insulin injection (subcutaneous group: 0.125 IU/g; intraperitoneal group: 0.250 IU/g) was injected before the first feeding, and biosynthetic human insulin injection (subcutaneous group: 0.075 IU/g; intraperitoneal group: 0.125 IU/g) was injected after a 0.5 h interval; the rest 3 times before feeding, the biosynthetic human insulin injection (subcutaneous group: 0.075 IU/g; intraperitoneal group: 0.125 IU/g) was injected for 4 weeks. The dietary intake, body mass, fasting blood glucose, and 1 and 2 h postprandial blood glucose of mice in each group were tested regularly, and an oral glucose tolerance test was performed.Results:The total dietary intake of mice in the intraperitoneal group was lower than that in the subcutaneous group. Compared with the initial body mass, the body mass of the mice in the subcutaneous and intraperitoneal groups decreased by 5.05 and 3.59 g at week 4, respectively. The changes of fasting blood glucose in the subcutaneous and intraperitoneal groups ranged from 5.4 to 9.4 and 5.4 to 6.4 mmol/L, respectively, and the changes of 1 h postprandial blood glucose ranged from 4.6 to 12.3 and 5.7 to 8.9 mmol/L, respectively, and the changes of 2 h postprandial blood glucose ranged from 2.5 to 9.8 and 3.8 to 7.1 mmol/L, respectively. For the glucose tolerance index, the intraperitoneal group showed improvement at all time points, and the subcutaneous group showed a decrease at all time points except for 0 and 60 min.Conclusions:In combination with dietary intervention, insulin intraperitoneal injection was more effective in controlling blood glucose in KKAy mice with spontaneous type 2 diabetes compared with subcutaneous insulin injection, and had a significant improvement in glucose tolerance.
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Objective:To study the effect of insulin intraperitoneal injection on abnormal blood lipid intype 2 diabetic KKAy mice.Methods:Type 2 diabetic mice model was established by feeding high fat and high sugar diet. KKAy model mice were randomly divided into intraperitoneal injection group ( n=6), subcutaneous injection group ( n=6) and no-treatment group ( n=3). At the same time, healthy C57BL/6J mice were selected as normal group ( n=6), and healthy KKAy mice as disease-free group ( n=6). The treatment process was divided into two stages. The first stage consists of 6 weeks, in which the mice in the intraperitoneal and subcutaneous groups were treated with insulin intraperitoneally and subcutaneously respectively. The second stage consists of 4 weeks, in which the mice in intraperitoneal and subcutaneous groups were subcutaneously injected with insulin. The mice in the remaining 3 groups were not treated. The changes of related indicators were detected every two weeks, including body weight, fasting blood sugar, 2 hours after meal blood sugar, triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). Results:Changing the injection solution in the medium term of the treatment had no effect on the body mass and blood sugar of KKAy mice with type 2 diabetes. Under this condition, the effect of intraperitoneal injection of insulin on HDL-C and LDL-C is significantly better than that of subcutaneous injection. Besides, both injection solutions are effective in regulating TG, but the effect of reducing total cholesterol is not obvious.Conclusions:The intraperitoneal injection of insulin has a certain effect on the blood lipid abnormality of type 2 diabetic KKAy mice. It can promote the increase of HDL-C, the decrease of LDL-C, and the decrease of TG.
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Under normal conditions,insulin secreted by the pancreas enters the liver through the portal vein,forming a difference in insulin concentration above the peripheral circulation.Subcutaneous administration of insulin forms a portal-peripheral concentration gradient of insulin above the liver,which is inconsistent with normal physiological conditions.Intraperitoneal insulin administration has been extensively investigated because that is closer to physiological state.In this paper,the pharmacokinetic and pharmacodynamic studies of insulin intraperitoneal administration were reviewed.Compared with the conventional subcutaneous delivery,intraperitoneal insulin administration can not only reduce the incidence of hypoglycemia,but also has the advantage of correcting abnormal lipid metabolism.This means that intraperitoneal administration of insulin has a positive effect on the prevention and treatment of diabetic complications.Therefore,it is necessary and feasible to develop a safe,low-cost,and easy-to-use percutaneous intraperitoneal insulin delivery device.
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Objective To establish a simple and gentle antigen loading method to prepare pH-responsive and biodegradable microcapsules for efficient antigen delivery.Methods Co-precipitation method was used to embed chicken egg albumin (OVA) in CaCO3 particles.Then,TA and Al (Ⅲ) were coated on the surface of CaCO3 particles template by metal-organic coordination bonds.The CaCO3 template was removed from disodium edetate to obtain TA-Al(Ⅲ) microcapsules carrying OVA,i.e.the OVA@TA-Al(Ⅲ) microcapsules.The microcapsules were characterized by field emission scanning electron microscopy,transmission electron microscopy,X-ray energy spectrometry and atomic force microscopy.The distribution of OVA in the microcapsules was observed by laser scanning confocal microscopy.The cumulative release rate of OVA in the microcapsules at different pH phosphate buffers was also investigated.The cytotoxicity of the microcapsules on immortalized mouse dendritic cells DC2.4 was observed by thiazolyl blue assay.The phagocytosis of the microcapsules by DC2.4 cells was observed by laser scanning confocal microscopy.Results The results of field emission scanning electron microscope and transmission electron microscopy showed that the OVA@TA-Al(Ⅲ) microcapsules have a intact structure and a hollow and collapsed appearance with a diameter of about 4 μm.X-ray energy spectrum showed that there are five kinds of elements,i.e.C,O,Al,Si and Na,in the microcapsules,among which C,Al and some O elements belong to the composition of the microcapsules.Atomic force microscopy showed that the microcapsules have an ultra-thin wall,and the walls of the microcapsules are uniform in thickness (about 16 nm).Laser scanning confocal microscopy showed that OVAs were evenly distributed in the CaCO3 particles.Moreover,the pH sensitivity of the coordination bond makes the OVA@TA-Al(Ⅲ) microcapsules have pH responsiveness.In addition,the microcapsules also have good biocompatibility,and the DC2.4 cells also have good phagocytic ability to the microcapsules.Conclusion A simple and gentle antigen-encapsuling method was developed to achieve effective antigen payload and pH responsive delivery.The prepared microcapsules are expected to be used as a novel antigen delivery vector for clinical research.
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Objective To prepare icariin-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (icariin nanoparticles) and analyze their physical and chemical properties,the release of icariin,and the effects on human osteoblast cells in vitro.Methods Icariin nanoparticles were prepared by ultrasonic emulsification and dialysis method and characterized by transmission electron microscopy and particle size analyzer.The release studies in vitro were adopted to evaluate the release-control features.Thiazolyl blue tetrazolium bromide (MTT),alkaline phophatase activity assay,and calcium nodes dyeing were carried out to investigate the effects of icariin nanoparticles on the growth and differentiation of human osteoblast cells MG-63.Results The icariin nanoparticles had spherical shapes and uniform particle size,and the mean size of the nanoparticles was (185.8±5.6) nm.The icariin nanoparticles showed the best property of sustained release and biocompatibility.Meanwhile,the icariin nanoparticles had no effect on the growth of MG-63 ceils,but they promote the differentiation of osteoblast cells by a concentration-and time-dependent manner.Conclusions The icariin nanoparticles prepared by ultrasonic emulsification and dialysis method have a good effect on the differentiation of human osteoblast cells in vitro and are biocompatible.
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Objective To prepare three kinds of biodegradable film materials used for protein drug carrier,and compare their degradation and drug release behavior.Methods Three different biodegradable and controlled release films,gelatin,chitosan oligosaccharides and crosslinked chitosan oligosaccharides films were prepared.Protein release behavior was determined by the Bradford.At the same time,degradation rate and swelling rate were tested,and the biocompatibility of film was investigated by MTT assay.Results The release time of crosslinked chitosan oligosaccharides film was 168 h,which was longer than that of chitosan oligosaccharides film,and different in different solution.The degradation rate and the swelling rate of crosslinked chitosan oligosaccharides was 60％ (360 h) and 110.45％,respectively,while the chitosan oligosaccharides membrane was 80％ (360 h) and 113.03％.The MTI assay revealed that the crosslinked chitosan oligosaccharides film had better biocompatibility.Conclusions By comparing different properties,the crosslinked chitosan oligosaccharides film is the best choice for protein drug carrier.
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Objective To develop paclitaxel-loaded polymeric micelles from poly (ε-caprolactone)-poly (ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL),and to evaluate in vitro cytotoxicity as well as in vivo antitumor activity against EMT-6 tumor breast cell.Methods Paclitaxel-loaded polymeric micelles were prepared by thin-film hydration and ultrasonic method.The physical status of paclitaxel inside the polymeric micelles was investigated by differential scanning calorimetry (DSC).In vitro cytotoxicity of paclitaxel-loaded polymeric micelles against EMT-6 cell line was assessed by MTT assay.In vivo anticancer activity was evaluated against EMT-6 tumorbearing mice,with commercially available Taxol injection as control.Results Paclitaxel-loaded polymeric micelles exhibited homogeneous spherical shapes with apparent core-shell morphology.The average diameter of paclitaxelloaded polymeric micelles was 93 nm.DSC study indicated that paclitaxel was in solid amorphous state after being encapsulated in the polymeric micelles.In vitro cytotoxicity demonstrated that the cytotoxic effect of paclitaxelloaded polymeric micelles was lower than that of Taxol injection at the same paclitaxel content.Paclitaxel-loaded polymeric micelles showed greater tumor growth-inhibition effect in vivo on EMT-6 breast tumor in comparison with that of Taxol injection,with tumor growth inhibition of 85.79％ and 63.37％,respectively (P＜0.05).Conculsions The prepared paclitaxel-loaded polymeric micelles showed high anti-tumoral efficacy and low toxicity,and might have the potential to be developed as an effective anticancer drug-delivery system for cancer chemotherapy.
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Polymersomes have attracted tremendous attention as novel drug delivery systems because of their unique and superior structure,tunable membrane properties,colloidal stability,and ability in encapsulating a broad range of both water soluble and insoluble substances.In this paper,preparation method and criteria for the formation of polymersomes,their structure and characterization as well as amphiphilic block copolymers for vesicle formation are addressed.Moreover,research progress on polymersomes as drug delivery system in the field of therapeutic and diagnostic applications are reviewed in this paper.
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ObjectiveTo observe the subcutaneous and intraperitoneal insulin injection's effect of the level of oxygen free radicals of type 2 diabetes model.MethodsC57BL/6J mice were chosen as normal control group (C group,n=9).KK mice were randomly divided into intraperitoneal injection of insulin group (i.p.group,n=9),the subcutaneous insulin group (s.c.group,n=9) and untreated group (U group,n =9).The i.p.group and the s.c.groups were given certain amount of insulin (insulin injecta and protamine insulin injecta by volume ratio of 2:1 mixture)for one month,maintained the GLU at normal levels (6±1.5) mmol/L.SOD,GSH-PX activity and MDA content of serum,liver,kidney and heart in each group were detected.Results The liver,kidney,heart and serum's SOD and GSH-PX activity significantly reduced and MDA content significantly increased in the U group.Both kinds of delivery methods could increase serum SOD and GSH-PX activity and reduce the content of MDA to the normal control group level,but the intraperitoneal injection had stronger effect.Two kinds of delivery methods could both reduce the MDA content of liver,and had almost the same effect; but the subcutaneous injection group had better effect on increasing the liver's SOD activity,and the intraperitoneal injection had better effect on increasing liver's GSH-PX activity.Intraperitoneal injection had better effect on reducing kidney' s MDA content and increased SOD activity.Two kinds of delivery methods had the same effect on reducing the heart's MDA content.Conclusion The two delivery methods can both make the MDA levels of KK mice in serum,heart,liver and kidney fall to as normal as that of control group,but the two delivery methods have different ways of improving the antioxidant capacity in different organs.Intraperitoneal injection can reduce MDA content in serum and kidney better.
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Objective To investigate the feasibility of using a novel docetaxel-loaded polycaprolactoneTween 80 (PCL-Tween 80) nanoparticles for glioma therapy.Methods Two types of docetaxel-loaded nanoparticles were made from commercial polycaprolactone (PCL) and a self-synthesized PCL-Tween 80 copolymer using a modified solvent extraction/evaporation method.A C6 glioma cell line was used to investigate the uptake of polymeric nanoparticles by brain cancer cells.In vitro cancer cell viability was assessed using MTT toxic assay.Results The nanoparticles were found by FESEM to have a spherical shape and be around 200 nm in diameter.The copolymers could encapsulate 10% of the drug in the nanoparticles and release 34.9% of the encapsulated drug over 28 days.The drug-loaded PCL-Tween 80 nanoparticles showed better in vitro cytotoxicity towards C6 cancer cells than Taxotere at the same drug concentration.Conclusion Nanoparticles using PCL-Tween 80 copolymer as drug delivery vehicles may have a promising outcome for glioma patients.
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VEGF nanoparticle (VEGF-NP) was prepared by a multi-emulsification technique using a biodegradable poly-dl-lactic-co-glycolic (PLGA) as matrix material. The nanoparticles were characterized for size, VEGF loading capacity, and in vitro release. VEGF-NP and naked VEGF plasmid were intramuscularly injected into the ischemia site of the rabbit chronic hindlimb ischemia model and the efficiency of VEGF-NP as gene delivery carrier for gene therapy in animal model was evaluated. Gene therapuetic effect was assessed evaluated by RT-PCR, immunohistochemistry and angiography assay. The average size of VEGF-NP was around 300 nm. The encapsulation efficiency of VEGF was above 96%. Loading amount of VEGF in the nanoparticles was about 4%. In vitro, nanoparticles maintained sustained-release of VEGF for two weeks. Two weeks post gene injection the capillary density in VEGF-NP group (81.22 per mm2) was significantly higher than that in control group (29.54 mm2). RT-PCR results showed greatly higher VEGF expression in VEGF-NP group (31.79au * mm) than that in naked VEGF group (9.15 au * mm). As a carrier system for gene therapy in animal model, VEGF-NP is much better than naked DNA plasmid. The results demonstrate great possibility of using NP carrier in human gene therapy.
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Animals , Rabbits , Disease Models, Animal , Gene Transfer Techniques , Genetic Therapy , Genetic Vectors , Chemistry , Lactic Acid , Chemistry , Nanoparticles , Chemistry , Plasmids , Polyglycolic Acid , Chemistry , Vascular Endothelial Growth Factor A , GeneticsABSTRACT
OBJECTIVE:To observe the efficacy of mifepristone-releasing implants for endometriosis in rats.METHODS:Mifepristone-releasing implants(one tube at 0.75,1.5,and 3.0 cm in length,or 2,3,4 tubes at 3 cm in length) were embedded subcutaneously in model rats with endometriosis.The inhibition ratio on the endometriosis was measured 3 months later and compared with the placebo control group.RESULTS:In vitro mean drug release rate of about 9 ?g?d-1 was achieved for the one-tube implant at 3 cm in length for the first 15 days,but reduced to 5 ?g?d-1 after 30 days and which was maintained for over 6 months.Inhibition ratios of(18.6?17.3)%,(31.5?12.7)% and(72.2?12.3)% on the growth of endometrial explants were achieved after subcutaneous implantation of mifepristone-releasing implants(1 tube at 1.5 cm or 3 cm in length or 2 tubes at 3.0 cm in length),showing significance differences as compared with control group(P